The Cytotoxic Cell Studies Group has made significant advances in our study of members of the murine Ly-49 family. Several novel Ly-49 cDNAs isolated from the 129 mouse strain have been cloned and characterized. An additional novel Ly-49 has been isolated from the CBA mouse strain. Two of the new Ly-49s we have isolated represent novel NK cell activation receptors (Ly-49P and Ly-49L). We have shown that these activating receptors associate with a novel signal transduction molecule (DAP-12) that is required for the generation of the activation signal. We have also completed a study linking STAT proteins to the induction of perforin gene transcription by cytokines in NK cells. The regulatory region of the human perforin gene was cloned and used to identify an STAT-binding element that is important for perforin promoter activity. Current studies are directed towards identifying additional molecules involved in the NK cell activation pathway. - Cytotoxicity, Gene regulation, immune response, Natural killer cells, receptors,